Translational and Clinical Neuroscience

Center for Autism and Neurodevelopment faculty employ brain imaging of human subjects combined with genetics to investigate the relationships between neuroanatomical features of patients and their genetic makeup. Because the genes and neurodevelopmental processes affected in autism and related disorders could serve as targets for new drugs, our faculty pursue the discovery and development of new drugs for autism and other neurodevelopmental disorders.

Dana Brazdziunas Lab

Developing programs in the early diagnosis and treatment of children with autism spectrum disorder and other related neurodevelopmental disorder.

Research Description

Brazdziunas research is focused on the development of state-of-the-art programs in the early diagnosis and treatment of children with autism spectrum disorder and other related neurodevelopmental disorder as well as teaching health care providers at all levels early recognition of developmental disorder including autism spectrum disorder.

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John Csernansky

Vivo neuroimaging of neuropsychiatric disorders, especially schizophrenia and Alzheimer disease, clinical trials of cognition-enhancing drugs, and the development of valid animal models for neuropsychiatric disorders.

Csernansky chairs the Department of Psychiatry and Behavioral Sciences and is the Lizzie Gilman Professor of Psychiatry and Behavioral Sciences. His research interests include in vivo neuroimaging of neuropsychiatric disorders, especially schizophrenia and Alzheimer disease, clinical trials of cognition-enhancing drugs, and the development of valid animal models for neuropsychiatric disorders.

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Tracy Gertler Lab

Research Description

The goal of my basic science research is to understand the mechanisms by which genetic ion channel variants identified in patients with early-onset epilepsy translate to altered channel biophysics when isolated in an expression system, to abnormal intrinsic neuronal excitability when studied in patient-derived neurons (made from induced pluripotent stem cell lines), and to circuit-level disruption resulting in epileptogenesis in transgenic animal models. This three-pronged approach shares a common pathophysiologic protein, and is intended to identify new therapeutic targets by complementary ion channel, neuronal, and synaptic modulation

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Herbert Meltzer Lab

Studying basic and clinical psychopharmacology, pharmacogenomics, and prevention of suicide.

Research Description

Meltzer is the director of the Translational Neuropharmacology Program at Feinberg. His research interests include research interests include: basic and clinical psychopharmacology, pharmacogenomics, and prevention of suicide.

John Millichap Lab

Utilizes a multidisciplinary team approach to the diagnosis and treatment of pediatric epilepsy and comorbidities

Research Description

Dr. Millichap has over 40 peer-reviewed medical publications and serves as the Section Editor of the Resident and Fellow Section of the journal Neurology and the Editor of Pediatric Neurology Briefs. As a member of the academic faculty of Northwestern University, he is involved in the education of trainees and grant-funded clinical research concerning epileptic encephalopathies.

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Peter Penzes Lab

Studying the molecular and cellular mechanisms that control the formation and modification of dendritic spines in the mammalian brain

Research Description

Research in my laboratory centers on the molecular and cellular mechanisms that control the formation and modification of dendritic spines in the mammalian brain. These mechanisms underlie the normal development and plasticity of the brain, and contribute to higher brain functions, including cognitive, social, and communication behavior. However, when these mechanisms go awry, they lead to mental and neurological disorders. Our analysis integrates multiple organizational levels, from molecular, cellular, circuit, and rodent models, to human subjects. We employ both a “translational” strategy, utilizing basic mechanistic data we generate to understand disease pathogenesis, and a “reverse-translational” strategy, in which genetic, neuropathological, and imaging studies in human subjects help guide the discovery of novel mechanistic insight. The ultimate goal of these studies is to develop therapeutic approaches to prevent or reverse neuropsychiatric disorders, by targeting mechanisms that control dendritic spines and synapses.

Projects within Our Lab

1. Mechanistic studies on the molecular mechanisms of dendritic spine plasticity. This line of research aims to identify and elucidate functions of novel molecular regulators of synaptic circuit modification during the lifespan. We investigate the formation, remodeling, and elimination of spiny synapses in neurons using both in vitro and in vivo models. We are particularly interested in signaling, adhesion, and scaffolding molecules that control cell-to-cell communication and mediate intracellular signaling by neurotransmitter receptors. My laboratory continues to investigate small GTPase pathways and the roles of guanine-nucleotide exchange factors, such as kalirin and Epac2, and their downstream targets Rac, PAK, Rap and Ras. In addition, we have made important contributions to understanding how synaptic activity controls synapse size and strength through a pathway involving NMDA receptors, CaMKII, kalirin, Rac1 and actin, how rapid synaptic plasticity in the brain is regulated by locally synthesized estrogen, how adhesion molecules including N-cadherin control synapse size and strength, and how dopamine and neuroligin control synapse stability though Epac2 and Rap1.

2. Translational and reverse-translational studies on the molecular substrates of dendritic spine pathology. Investigations of genetic, neuropathological, and neuromorphological alterations in human subjects with psychiatric disorders have started to reveal the pathogenic mechanisms behind these illnesses, and are also guiding the discovery of unexpected basic mechanisms of brain development and function. Through studies performed in the lab and through collaborations, we investigate molecular and cellular alterations occurring in patients with schizophrenia, bipolar disorder, autism, and Alzheimer’s disease. We then use model systems, such as neuronal cultures or mice, to elucidate the functions and pathogenic mechanisms of key molecules. We are currently investigating the basic synaptic functions of several leading mental disorder risk genes, to understand how they contribute to normal brain function and to synapse pathology. Conversely, many molecules we have been studying in the lab have more recently been implicated in the pathogenesis of mental disorders through independent neuropathological or genetic studies. We have shown that molecules that control basic synapse structural plasticity, such as kalirin and Epac2, functionally interact with leading mental disorder risk molecules, such as neuregulin1, ErbB4, DISC1, 5HT2A receptors, dopamine receptors, neuroligin, and Shank3. We have generated mutant mice in which kalirin or Epac2 are ablated, and have shown that these molecules control behaviors relevant for mental disorders, such as sociability, working memory, sensory motor gating, and vocalizations. These animal models can thus help to understand the synaptic substrates of specific aspects of mental disorders. To investigate the abnormal regulation of these molecular pathways in schizophrenia, autism, Alzheimer’s disease, and the impact of these molecular abnormalities on disease phenotypes in human subjects, we are collaborating with neuropathologists, brain imaging experts, and geneticists who investigate human subjects.

Potential Clinical Implications of Our Work

Therapeutic reversal of neuropsychiatric disease by targeting synaptic connectivity. By harnessing the knowledge from our basic and reverse-translational studies, my goal is to develop novel therapeutic approaches to prevent, delay, or reverse the course of mental and neurodegenerative disorders. Because abnormal synaptic connections play central roles in the pathogenesis of schizophrenia, autism, and Alzheimer’s disease, pharmacological targeting of key molecules implicated in synaptic plasticity and pathology can rescue disease associated abnormalities, and thereby influence the outcome of the disease. We are currently developing transgenic animal models to validate synaptic signaling molecules as therapeutic targets in mental disorders. We are also developing cellular assays which we will use in high-throughput screens for small-molecule regulators of synapse remodeling. Our goal is to identify small-molecule regulators of synapse remodeling which can be taken into clinical trials as therapeutics aimed at reversing synaptic deficits, and thus cognitive dysfunction, in mental disorders.

Our Facilities

In our studies, we employ a multidisciplinary approach, using an array of methods that include advanced cellular and in vivo microscopy, biochemistry, electrophysiology, manipulations of gene expression in vivo, mouse behavioral analysis, circuit mapping, and human genetics and neuropathology.

Graduate Students

Technical Staff

Visiting Scholar

Temporary Staff

Lei Wang Lab

Developing multidimensional and multimodal neuroimaging biomarkers using the tools of computational anatomy.

Research Description

Lei Wang's lab research is focused on the development of multidimensional and multimodal neuroimaging biomarkers using the tools of computational anatomy. Working with collaborators from engineering, mathematics, psychology and clinical specialties, the team focuses on the following major areas: Mapping of Brain Structures using MRI. Dr. Wang develops automated pipelines to delineate brain structures based on simultaneous mappings of multiple structures from multiple atlases. This includes deep brain structures (such as the hippocampus, amygdala, thalamus, and basal ganglia) and cortical structures.Complex Neuroimaging Biomarkers. They develop modeling and statistical approaches for the analysis of these maps and frameworks for joint, integrated analyses of multidimensional, multimodal information based on the structural mapping of the brain.